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Gene Review

Fos  -  FBJ osteosarcoma oncogene

Mus musculus

Synonyms: Cellular oncogene fos, D12Rfj1, Proto-oncogene c-Fos, c-fos, cFos
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Disease relevance of Fos


Psychiatry related information on Fos


High impact information on Fos

  • In response to receptor activation, betaarr1 translocates to the nucleus and is selectively enriched at specific promoters such as that of p27 and c-fos, where it facilitates the recruitment of histone acetyltransferase p300, resulting in enhanced local histone H4 acetylation and transcription of these genes [11].
  • The immediate early gene (IEG) c-fos encodes a transcription factor [12].
  • To address this issue, we generated a mouse in which c-fos expression is largely eliminated in the hippocampus [12].
  • Although c-fos is induced by neuronal activity, including kainic acid-induced seizures, whether and how c-fos is involved in excitotoxicity is still unknown [12].
  • Emerging evidence suggests that c-fos is essential in regulating neuronal cell survival versus death [12].

Chemical compound and disease context of Fos


Biological context of Fos


Anatomical context of Fos


Associations of Fos with chemical compounds

  • We showed previously that AP-1 complexes are activated during the proliferative response that parallels the development of renal lesions after nephron reduction, but little is known about the specific role of individual Jun/Fos components in the deterioration process [24].
  • We demonstrate that transient exposure to FGF-1 results in a significant decrease in Fos transcript expression and a decrease in tyrosine phosphorylation of the FGFR-1, p42(mapk), and p44(mapk) [25].
  • This effect is likely to be elicited by the dimerization potential of the Jun leucine zipper trapping cellular Jun and/or Fos in a protein complex unable to bind to DNA [26].
  • The redox function of Ref-1 involves reduction of oxidized cysteine residues within the DNA binding domains of several transcription factors, including Fos and Jun. Reduction of these residues is required for DNA binding, providing a redox-dependent mechanism for regulation of target gene expression [27].
  • Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium [28].

Physical interactions of Fos

  • Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1 [29].
  • Coexpression of the cAMP-responsive element-binding protein-binding protein and steroid receptor coactivator-1a further enhanced the Fos/Jun-mediated transcription [30].
  • These data provide evidence that Fos/Jun transcription factor complexes play a role in modulating both myeloid cell survival and differentiation and suggest that genetic lesions that alter Fos expression may cooperate with deregulated c-Myc in leukemogenesis [31].
  • We have identified a MyoD-binding site overlapping with the serum-responsive element in the c-fos promoter [32].
  • We have investigated the ability of Fos/Jun (a transcriptional activator involved in the signal transduction pathway) to interact with its cognate binding site located in the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when this site was reconstituted into a nucleosome [33].

Enzymatic interactions of Fos


Co-localisations of Fos


Regulatory relationships of Fos

  • Thus an autoregulatory mechanism operates-the RANKL-induced c-Fos induces its own inhibitor [19].
  • Here we report that Rb can repress c-fos expression and AP-1 transcriptional activity in both serum-induced and cycling 3T3 cells [39].
  • Functionally, Djun in cooperation with mouse c-fos can trans-activate activator protein 1 DNA binding site when introduced into mammalian cells [40].
  • Another mutant, with a C-terminal deletion of 30 amino acids, retained the ability to activate a tyrosine kinase and to induce c-myc expression but lost the ability to induce c-fos and c-jun expression [41].
  • Antisense oligonucleotide to c-fos gene inhibited the cytokine-induced JE/MCP-1 gene expression in the cells [42].
  • Dimerization with the Jun proteins inhibits c-Fos nuclear exit [43].

Other interactions of Fos

  • Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation [1].
  • In contrast, Fos and Jun, but not Myc, rescued the block induced by dominant negative Ras [44].
  • Mutation of an autophosphorylation site at tyrosine 809 in the cytoplasmic domain of human CSF-1R does not significantly reduce its ligand-stimulated tyrosine kinase activity, binding to phosphatidylinositol 3-kinase, or induction of the immediate early response genes, c-fos and junB (ref.2) [45].
  • This IFN-beta gene induction mechanism is distinct from that induced by virus, and is dependent on c-Fos itself [19].
  • Comparison of several myogenin mutants for their responsiveness to Fos and Jun shows that repression is directed at the basic-HLH region [46].

Analytical, diagnostic and therapeutic context of Fos


  1. Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation. Matsuo, K., Owens, J.M., Tonko, M., Elliott, C., Chambers, T.J., Wagner, E.F. Nat. Genet. (2000) [Pubmed]
  2. c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. Wang, Z.Q., Liang, J., Schellander, K., Wagner, E.F., Grigoriadis, A.E. Cancer Res. (1995) [Pubmed]
  3. Activator protein 1 transcription factors are fundamental to v-rasHa-induced changes in gene expression in neoplastic keratinocytes. Rutberg, S.E., Adams, T.L., Glick, A., Bonovich, M.T., Vinson, C., Yuspa, S.H. Cancer Res. (2000) [Pubmed]
  4. Defective induction of Jun and Fos-related proteins in phorbol ester-resistant EL4 mouse thymoma cells. Jensen, D.E., Frankis, R.C., Sando, J.J. Oncogene (1991) [Pubmed]
  5. Ultraviolet irradiation, although it activates the transcription factor AP-1 in F9 teratocarcinoma stem cells, does not induce the full complement of differentiation-associated genes. Auer, H.P., König, H., Litfin, M., Stein, B., Rahmsdorf, H.J. Exp. Cell Res. (1994) [Pubmed]
  6. Region-specific changes in immediate early gene expression in response to sleep deprivation and recovery sleep in the mouse brain. Terao, A., Greco, M.A., Davis, R.W., Heller, H.C., Kilduff, T.S. Neuroscience (2003) [Pubmed]
  7. Glutamate receptor agonists increase the expression of Fos, Fra, and AP-1 DNA binding activity in the mammalian brain. Sonnenberg, J.L., Mitchelmore, C., Macgregor-Leon, P.F., Hempstead, J., Morgan, J.I., Curran, T. J. Neurosci. Res. (1989) [Pubmed]
  8. Sensitized increase of period gene expression in the mouse caudate/putamen caused by repeated injection of methamphetamine. Nikaido, T., Akiyama, M., Moriya, T., Shibata, S. Mol. Pharmacol. (2001) [Pubmed]
  9. Effects of prolonged wakefulness on c-fos and AP1 activity in young and old rats. Basheer, R., Shiromani, P.J. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  10. Sleep and wakefulness in c-fos and fos B gene knockout mice. Shiromani, P.J., Basheer, R., Thakkar, J., Wagner, D., Greco, M.A., Charness, M.E. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  11. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Kang, J., Shi, Y., Xiang, B., Qu, B., Su, W., Zhu, M., Zhang, M., Bao, G., Wang, F., Zhang, X., Yang, R., Fan, F., Chen, X., Pei, G., Ma, L. Cell (2005) [Pubmed]
  12. c-fos regulates neuronal excitability and survival. Zhang, J., Zhang, D., McQuade, J.S., Behbehani, M., Tsien, J.Z., Xu, M. Nat. Genet. (2002) [Pubmed]
  13. Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. Schadendorf, D., Kern, M.A., Artuc, M., Pahl, H.L., Rosenbach, T., Fichtner, I., Nürnberg, W., Stüting, S., von Stebut, E., Worm, M., Makki, A., Jurgovsky, K., Kolde, G., Henz, B.M. J. Cell Biol. (1996) [Pubmed]
  14. Differential regulation by c-jun and c-fos protooncogenes of hormone response from composite glucocorticoid response element in human papilloma virus type 16 regulatory region. Mittal, R., Kumar, K.U., Pater, A., Pater, M.M. Mol. Endocrinol. (1994) [Pubmed]
  15. Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription. Watters, J.J., Campbell, J.S., Cunningham, M.J., Krebs, E.G., Dorsa, D.M. Endocrinology (1997) [Pubmed]
  16. Expression of c-fos precedes MDR3 in vincristine and adriamycin selected multidrug resistant murine erythroleukemia cells. Bhushan, A., Slapak, C.A., Levy, S.B., Tritton, T.R. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  17. Constitutive overexpression of the c-fos gene in radiation-induced granulocytic leukemia in mice. Ishihara, H., Yoshida, K., Nemoto, K., Tsuneoka, K., Shikita, M. Radiat. Res. (1993) [Pubmed]
  18. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Chiu, R., Angel, P., Karin, M. Cell (1989) [Pubmed]
  19. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Takayanagi, H., Kim, S., Matsuo, K., Suzuki, H., Suzuki, T., Sato, K., Yokochi, T., Oda, H., Nakamura, K., Ida, N., Wagner, E.F., Taniguchi, T. Nature (2002) [Pubmed]
  20. Regulation of proenkephalin by Fos and Jun. Sonnenberg, J.L., Rauscher, F.J., Morgan, J.I., Curran, T. Science (1989) [Pubmed]
  21. Nuclear factor of activated T cells contains Fos and Jun. Jain, J., McCaffrey, P.G., Valge-Archer, V.E., Rao, A. Nature (1992) [Pubmed]
  22. Fra-1 replaces c-Fos-dependent functions in mice. Fleischmann, A., Hafezi, F., Elliott, C., Remé, C.E., Rüther, U., Wagner, E.F. Genes Dev. (2000) [Pubmed]
  23. Osteoblasts are target cells for transformation in c-fos transgenic mice. Grigoriadis, A.E., Schellander, K., Wang, Z.Q., Wagner, E.F. J. Cell Biol. (1993) [Pubmed]
  24. JunD protects against chronic kidney disease by regulating paracrine mitogens. Pillebout, E., Weitzman, J.B., Burtin, M., Martino, C., Federici, P., Yaniv, M., Friedlander, G., Terzi, F. J. Clin. Invest. (2003) [Pubmed]
  25. Activation of the MAP kinase pathway by FGF-1 correlates with cell proliferation induction while activation of the Src pathway correlates with migration. LaVallee, T.M., Prudovsky, I.A., McMahon, G.A., Hu, X., Maciag, T. J. Cell Biol. (1998) [Pubmed]
  26. Transformation and transactivation suppressor activity of the c-Jun leucine zipper fused to a bacterial repressor. Granger-Schnarr, M., Benusiglio, E., Schnarr, M., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  27. Cysteine 64 of Ref-1 is not essential for redox regulation of AP-1 DNA binding. Ordway, J.M., Eberhart, D., Curran, T. Mol. Cell. Biol. (2003) [Pubmed]
  28. Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle. Miao, G.G., Curran, T. Mol. Cell. Biol. (1994) [Pubmed]
  29. Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. Northrop, J.P., Ullman, K.S., Crabtree, G.R. J. Biol. Chem. (1993) [Pubmed]
  30. Identification of a functional AP1 element in the rat vasopressin gene promoter. Yoshida, M., Iwasaki, Y., Asai, M., Takayasu, S., Taguchi, T., Itoi, K., Hashimoto, K., Oiso, Y. Endocrinology (2006) [Pubmed]
  31. Fos modulates myeloid cell survival and differentiation and partially abrogates the c-Myc block in terminal myeloid differentiation. Shafarenko, M., Amanullah, A., Gregory, B., Liebermann, D.A., Hoffman, B. Blood (2004) [Pubmed]
  32. Repression of c-fos promoter by MyoD on muscle cell differentiation. Trouche, D., Grigoriev, M., Lenormand, J.L., Robin, P., Leibovitch, S.A., Sassone-Corsi, P., Harel-Bellan, A. Nature (1993) [Pubmed]
  33. The binding of a Fos/Jun heterodimer can completely disrupt the structure of a nucleosome. Ng, K.W., Ridgway, P., Cohen, D.R., Tremethick, D.J. EMBO J. (1997) [Pubmed]
  34. Activation of ternary complex factor Elk-1 by stress-activated protein kinases. Gille, H., Strahl, T., Shaw, P.E. Curr. Biol. (1995) [Pubmed]
  35. Trichostatin A activates the osteopontin gene promoter through AP1 site. Sakata, R., Minami, S., Sowa, Y., Yoshida, M., Tamaki, T. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  36. Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro. Curran, T., Gordon, M.B., Rubino, K.L., Sambucetti, L.C. Oncogene (1987) [Pubmed]
  37. Control of cell cycle gene expression in bone development and during c-Fos-induced osteosarcoma formation. Sunters, A., McCluskey, J., Grigoriadis, A.E. Dev. Genet. (1998) [Pubmed]
  38. Effects of leptin on corticotropin-releasing factor (CRF) synthesis and CRF neuron activation in the paraventricular hypothalamic nucleus of obese (ob/ob) mice. Huang, Q., Rivest, R., Richard, D. Endocrinology (1998) [Pubmed]
  39. Negative regulation of human c-fos expression by the retinoblastoma gene product. Robbins, P.D., Horowitz, J.M., Mulligan, R.C. Nature (1990) [Pubmed]
  40. Drosophila homolog of the mammalian jun oncogene is expressed during embryonic development and activates transcription in mammalian cells. Zhang, K., Chaillet, J.R., Perkins, L.A., Halazonetis, T.D., Perrimon, N. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  41. Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways. Asao, H., Takeshita, T., Ishii, N., Kumaki, S., Nakamura, M., Sugamura, K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  42. Retinoic acid suppression of c-fos gene inhibits expression of tumor necrosis factor-alpha-induced monocyte chemoattractant JE/MCP-1 in clonal osteoblastic MC3T3-E1 cells. Hanazawa, S., Takeshita, A., Kitano, S. J. Biol. Chem. (1994) [Pubmed]
  43. Heterodimerization with Jun family members regulates c-Fos nucleocytoplasmic traffic. Malnou, C.E., Salem, T., Brockly, F., Wodrich, H., Piechaczyk, M., Jariel-Encontre, I. J. Biol. Chem. (2007) [Pubmed]
  44. Myc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src. Barone, M.V., Courtneidge, S.A. Nature (1995) [Pubmed]
  45. Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signalling. Roussel, M.F., Cleveland, J.L., Shurtleff, S.A., Sherr, C.J. Nature (1991) [Pubmed]
  46. Fos and Jun repress transcriptional activation by myogenin and MyoD: the amino terminus of Jun can mediate repression. Li, L., Chambard, J.C., Karin, M., Olson, E.N. Genes Dev. (1992) [Pubmed]
  47. Regulation of AP-1 expression and activity in antigen-stimulated mast cells: the role played by protein kinase C and the possible involvement of Fos interacting protein. Lewin, I., Nechushtan, H., Ke, Q., Razin, E. Blood (1993) [Pubmed]
  48. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Zhao, Y., Xue, Y., Oberley, T.D., Kiningham, K.K., Lin, S.M., Yen, H.C., Majima, H., Hines, J., St Clair, D. Cancer Res. (2001) [Pubmed]
  49. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. Matsuo, K., Galson, D.L., Zhao, C., Peng, L., Laplace, C., Wang, K.Z., Bachler, M.A., Amano, H., Aburatani, H., Ishikawa, H., Wagner, E.F. J. Biol. Chem. (2004) [Pubmed]
  50. Apoptosis during castration-induced regression of the prostate is Fos dependent. Feng, Z., Joos, H.J., Vallan, C., Mühlbauer, R., Altermatt, H.J., Jaggi, R. Oncogene (1998) [Pubmed]
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